PRMT5在妇科恶性肿瘤中的研究进展

doi:10.12280/gjszjk.20240518

摘要/Abstract

摘要：

蛋白质精氨酸甲基转移酶5（protein arginine methyltransferase 5，PRMT5）是PRMT家族的主要成员，可催化组蛋白和非组蛋白中的精氨酸残基甲基化修饰，从而影响转录、RNA剪接、DNA修复、细胞周期控制等生物学过程。当前已有研究显示，PRMT5与人类恶性肿瘤的发生发展密切相关，发挥着类似致癌基因的作用。卵巢癌、宫颈癌和子宫内膜癌作为妇科三大恶性肿瘤，对女性生命健康构成了严重威胁。PRMT5在卵巢癌、宫颈癌和子宫内膜癌中表达上调，可促进肿瘤细胞的克隆形成、DNA复制和增殖能力。通过上皮-间质转化依赖的方式调控肿瘤细胞迁移，PRMT5可增强宫颈癌细胞上程序性死亡受体配体1（programmed death ligand-1，PD-L1）的稳定性和表达，从而促进肿瘤免疫逃逸。此外，PRMT5抑制剂与表观遗传药物联合应用可促进肿瘤细胞衰老，增强卵巢癌细胞对多西他赛的化疗敏感性，与多腺苷二磷酸核糖聚合酶[poly (ADP-ribose) polymeras，PARP]抑制剂协同抑制卵巢癌细胞的生长和增殖，并减轻PARP抑制剂带来的不良反应，用于卵巢癌的维持治疗，有望为妇科恶性肿瘤的治疗和预后提供新的思路。

关键词: 蛋白质精氨酸N-甲基转移酶, 宫颈肿瘤, 卵巢肿瘤, 子宫内膜肿瘤, 上皮-间质转化

Abstract:

Protein arginine methyltransferase 5 (PRMT5), a major member of the PRMT family, catalyzes the methylation of arginine residues in both histone and non-histone proteins. PRMT5 is involved in many biological processes such as transcription, RNA splicing, DNA repair, and cell cycle control. Current studies have shown that PRMT5 is closely related to the occurrence and development of human malignant tumors and plays a similar role as an oncogene. Ovarian cancer, cervical cancer and endometrial cancer, as the three major gynecological malignancies, pose a serious threat to women's life and health. The up-regulated PRMT5 in ovarian cancer, cervical cancer and endometrial cancer can promote the clonal formation, DNA replication and proliferation of tumor cells. By regulating the tumor cell migration in an EMT-dependent manner, PRMT5 can enhance the stability and expression of programmed death ligand-1 (PD-L1) on cervical cancer cells, thus promoting tumor immune escape. In addition, PRMT5 inhibitor combined with epigenetic drugs can promote tumor cell senescence, enhance the chemotherapy sensitivity of ovarian cancer cells to docetaxel, cooperate with poly (ADP-ribose) polymeras (PARP) inhibitors to inhibit the growth and proliferation of ovarian cancer cells, and reduce the adverse reactions caused by PARP inhibitors, suggesting that PRMT5 inhibitor can be used for maintenance treatment of ovarian cancer. It is expected to provide new ideas for the treatment and prognosis of gynecological malignant tumors.

Key words: Protein-arginine N-methyltransferases, Uterine cervical neoplasms, Ovarian neoplasms, Endometrial neoplasms, Epithelial-mesenchymal transition

宋萌萌, 陈芳, 包香香, 田馨莉. PRMT5在妇科恶性肿瘤中的研究进展[J]. 国际生殖健康/计划生育杂志, 2025, 44(2): 171-176.

SONG Meng-meng, CHEN Fang, BAO Xiang-xiang, TIAN Xin-li. Research Progress of PRMT5 in Gynecological Malignant Tumors[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(2): 171-176.

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